Transient protein-protein interactions modulate a very large range of biochemical processes. The importance of understanding protein-protein interactions goes well beyond fundamental basic science, as these interactions may well be important drug targets in addition to enzyme active sites, especially in relation to infectious diseases. The studies of protein-protein interactions proposed here address two long-term goals. First, to determine the basic structural, dynamic and chemical motifs that are central to biological recognition and specificity in protein-protein interactions. Our approach toward accomplishing this goal tests a model for the interaction of c-type cytochromes with their physiologically relevant electron donors and acceptors, and takes particular advantage of a new technology, plasmon waveguide resonance. This technology permits studies under conditions which mimic the in vivo conditions. We believe that the results of the proposed studies will provide fundamental mechanistic information that is broadly applicable to other, in many cases more complex or less tractable systems. Second, taking advantage of the availability of the Rhodobacter sphaeroides genome sequence and utilizing genomic based technologies (microarray and lacZ fusions) we will determine the regulation and expression of the twenty six c-type cytochromes in the Rhodobacter sphaeroides genome. The proposed studies will identify reaction partners and pathways previously unknown and greatly expand our understanding of the diversity of mechanisms used to control recognition and specificity in metabolic function. The growing resistance to antibiotics makes it imperative that we better understand microbial physiology/biochemistry in order to develop novel strategies to address bacterial infections. Thus, currently uncharacterized pathways not used by mammals may eventually be exploited for drug intervention and/or for environmental bioremediation.